Studies on Cycloheximide-Related Compounds. I Esters of Cycloheximide and their Antitoxoplasmic Activity

Abstract

Cycloheximide was isolated by Whiffen, Bohonos and Emerson^1l) from streptomycin culture of S. griseus, and its structure was elucidated by Kornfeld et al²⁾. The absolute configuration of the antibiotic was recently elucidated on the basis of optical rotatory dispersion and n.m.r. analysis by Djerassi and coworkers³⁾, Okuda and Suzuki⁴⁾ and Starkovsky and Johnson⁵⁾. The antibiotic has been used as an agricultural fungicide, rat-repellent and a drug against Cryptococcus meningitis. The antibiotic moreover has antitumor and antiprotozoa activities, however, its applications are restricted within narrow limits owing to considerable toxicity to plants and animals.

The purpose of this investigation is to synthesize more useful derivatives of cycloheximide. The present paper deals with the preparations and properties of a number of esters of the antibiotic and presents the evaluation of their antitoxoplasmic activities.